Table 2.
Highlights and strategy of endogenous repair
| Ref. | Cells, biomaterial, and medicine | Highlights and strategy |
| Human | ||
| Liu et al[35], 2016 | Amiloride | The biological behavior of NP-MSCs could be inhibited by acidic conditions, and amiloride may meliorate IVD degeneration by improving the activities of NP-MSCs. |
| Li et al[36], 2017 | NP-SCs | NP-SCs keep the regeneration ability similar to BMSCs with superior capacity in chondrogenesis. |
| Li et al[37], 2018 | Modified notochordal cell-rich NP explants | Modified notochordal cell-rich NP explants can attenuate degeneration and senescence of NP-MSC induced by TNF-α. |
| Jia et al[38], 2017 | D-NP-MSCs/ND-NP-MSCs | D-NP-MSCs displayed decreased biological characteristics compared with NP-MSCs. |
| Wu et al[40], 2017 | D-NP-MSCs/UCMSCs | D-NP-MSCs had lower expression of phenotype markers and exhibited reduced proliferation capability and differentiation potentials compared with UCMSCs. |
| Wang et al[41], 2016 | NPSCs/AFSCs/CESCs | A comparison of the osteogenic capacities: CESCs > AFSCs > BM-MSCs > NPSCs; for adipogenesis: BM-MSCs > NPSCs > CESCs > AFSCs; in chondrogenesis: CESCs > AFSCs > BMSCs > NPSCs. |
| Liang et al[42], 2018 | NP-MSCs | The biological behavior of NP-MSCs could be inhibited by compression loading. |
| Daisuke et al[43], 2012 | NPPCs | The frequency of Tie2+ cells decreases markedly in tissue with age and degeneration of the IVD, suggesting exhaustion of their capacity for regeneration. |
| Chen et al[44], 2018 | ICA | The addition of ICA to the conventional freezing medium could improve the viability and function of cryopreserved human NP-MSCs. |
| Quan et al[48], 2015 | MSC-like cells from NP | NP tissue contains MSC-like cells which could be isolated and proliferate in vitro. |
| Liu et al[49], 2017 | AF-MSCs, NP-MSCs, CEP-MSCs | AF-MSCs, NP-MSCs, and CEP-MSCs showed similar multilineage differentiation abilities; CEP-MSCs have the most powerful properties of migration and invasion when compared with AF-MSCs and NP-MSCs. |
| Blanco et al[27], 2010 | NP-MSCs | NP-MSCs were quite similar to BM-MSCs, with the exception that NP-MSCs are not able to differentiate into adipocytes. |
| Lazzarini et al[50], 2018 | NP-MSCs | NP-MSCs have the capacity of neuronal differentiation and could express neural markers without any electric functional properties. |
| Pereira et al[51], 2016 | CEP-MSCs | MSCs from CEP promote IVD regeneration by remodeling ECM. |
| Qi et al[57], 2018 | MSC-CM | MSC-CM has potential to alleviate HG induced cell cycle arrest and ECM degradation of NP-MSCs via p38 MAPK pathway. |
| Li et al[64], 2018 | CsA | CsA efficiently inhibited compression-induced NP-MSCs apoptosis by alleviating mitochondrial dysfunction and oxidative stress. |
| Rat | ||
| Zhao et al[34], 2017 | NP-MSCs | The efficacy of NP-MSCs is compromised by age, and old NP-MSCs displayed senescent features. |
| Li et al[39], 2019 | NP-MSCs | The MSC-CM + CC method (MSC complete medium culture + cloning cylinder) is a more reliable and efficient way for isolating and purifying NP-MSCs. |
| Li et al[45], 2013 | NP-MSCs | Compared to AD-MSCs, NP-MSCs showed greater viability, proliferation, and chondrocytic differentiation under hypoxia. |
| Wang et al[46], 2019 | Injectable hydrogel-loaded NP-MSCs | Injectable hydrogel-loaded NP-MSCs transplantation can delay the level of IVD degeneration and promote the regeneration of the degenerative IVD in a rat model. |
| Nan et al[52], 2019 | Nar | Nar efficiently attenuated H2O2-induced NP-MSCs apoptosis and mitochondrial dysfunction through PI3/AKT pathway. |
| Han et al[29], 2014 | NP-MSCs | An acidic environment is a major obstacle for IVD regeneration by AD-MSCs or NP-MSCs; NP-MSCs appeared less sensitive to inhibition by acidic PH. |
| Tao et al[28], 2013 | NPCs-NP-MSCs co-culture | NP-MSCs could tolerate IVD-like high osmolarity and NPCs-NP-MSCs co-culture increased cell proliferation and the expression of SOX-9, aggrecan, and collagen-II. |
| Tao et al[53], 2015 | TGF-β3/IGF-1 | The synergy between TGF-β3 and IGF-1 enhanced NP-MSCs viability, ECM biosynthesis, and differentiation towards NPCs by activating the MAPK/ERK signaling pathway. |
| Liu et al[30], 2019 | N-NP-MSCs/D-NP-MSCs | N-NP-MSCs showed a significantly higher proliferation rate, better stemness maintenance ability, but reduced cell apoptosis rate compared with D-NP-MSCs. |
| Li et al[55], 2018 | NP-MSCs | Hyperosmolarity of the IVD significantly inhibited the proliferation and chondrogenic differentiation of NP-MSCs by activating the ERK pathway. |
| Cheng et al[56], 2019 | TNF-α | Treatment with a high concentration of TNF-α (50-200 ng/mL) could induce apoptosis of NP-MSCs, whereas a relatively low TNF-α concentration (0.1-10 ng/mL) promoted the proliferation and migration of NP-MSCs, but inhibited their differentiation toward NP cells. |
| Lin et al[58], 2017 | L-PD of NP-MSCs | NP-MSCs at a L-PD (5 cells/cm2) have better biological characteristic, stronger multilineage differentiation, and higher expression of stem cell biomarkers compared with those at an M-PD (100 cells/cm2) and H-PD (10000 cells/cm2). |
| Yang et al[65], 2009 | BMSCs | BMSCs could arrest the degeneration of the murine notochordal NP and contribute to the augmentation of the ECM in the NP by both autonomous differentiation and stimulatory action on endogenous cells. |
| Liu et al[68], 2019 | NP-MSCs | High glucose concentration significantly decrease vitality, migration, and stemness of NP-MSCs. |
| Zhang et al[69], 2015 | NP-MSCs | The chondrogenic ability of NP-MSCs and BM-MSCs was similar under induction in vitro. |
| Dog | ||
| Erwin et al[47], 2013 | NPPCs | NPPCs have higher expression of the Nanog gene compared to MSCs and are capable of differentiation along chondrogenic, adipogenic, and neurogenic lineages in vitro and into oligodendrocyte, neuron, and astroglial specific precursor cells in vivo in the myelin-deficient shiverer mouse. |
| Bovine | ||
| Tekari et al[63], 2016 | NPPCs | The Tie2+ cells (NPPC) were spheroid in shape with capacity of multi-differentiation and may decline fast, which was partially reversed by FGF2 and hypoxic conditions. |
| Rabbit | ||
| Jia et al[54], 2018 | P-PRP/L-PRP | Both P-PRP and L-PRP could induce the proliferation and NP-differentiation of NP-MSCs; P-PRP could reduce the inflammatory and catabolic responses by avoiding the activation of the NF-κB pathway. |
| Rhesus macaque | ||
| Huang et al[66], 2013 | DPCs, SLRP | SLRP could reduce the susceptibility of DPCs to hypoxia-induced apoptosis via promoting the activation/stabilization of HIF-1α and HIF-2α. |
MSC: Mesenchymal stem cell; IVD: Intervertebral disc; NP: Nucleus pulposus; AF: Annulus fibrosus; CEP: Cartilaginous endplates; UCMSCs: Umbilical cord MSCs; AD: Adipose tissue; ECM: Extracellular matrix; ICA: Icariin; CM: Conditioned medium; HG: High glucose; CsA: Cyclosporine; Nar: Naringin; TGF-β3: Transforming growth factor beta 3; IGF: Insulin-like growth factor; TNF: Tumor necrosis factor; L-PD: Low plating density; NPPC: NP-derived progenitor cell; BM-MSC: Bone marrow mesenchymal stem cell; P-PRP: Pure platelet-rich plasma; L-PRP: Leukocyte-containing platelet-rich plasma; DPCs: Intervertebral disc progenitor cells; SLRP: Leucine-rich proteoglycans.